title: Effect of pressure sensitive adhesive and vehicles on permeation of terbinafine across porcine hoof membrane.
abstract: The purpose of this study was to investigate characteristics of transungual drug delivery and the feasibility of developing a drug-in-adhesive formulation of terbinafine. The permeation of terbinafine from a PSA matrix across porcine hoof membrane was determined using a plate containing poloxamer gel. The permeation rate of terbinafine across hairless mouse skin was evaluated using a flow-through diffusion cell system. The permeation of terbinafine across the hoof membranes was the highest from the silicone adhesive matrix, followed by PIB, and most of the acrylic adhesives, SIS, and SBS. The rank order of permeation rate across mice skin was different from the rank order across porcine hooves. The amount of terbinafine permeated across the porcine hoof membranes poorly correlated with the amount of terbinafine remaining inside the hooves after 20 days, however, the ratio between rate of terbinafine partitioning into the hoof membrane and its rate of diffusion across the membrane was relatively constant within the same type of PSA. For influence of various vehicles in enhancing permeation of terbinafine across the hoof membrane, all vehicles except Labrasol(®) showed tendency to improve permeation rate. However, the enhancement ratio of a given vehicle differed from one adhesive to another with a moderate correlation between them. The infrared spectrum of the hoof treated with NMP, PPG 400 or PEG 200 indicated that the conformation of keratin changed from a non-helical to a helical structure.
authors.affiliation: GTx, Inc., Memphis, TN, USA.
authors.forename: Tai Sang
authors.initials: TS
authors.lastname: Ahn
authors.forename: Jung-Phil
authors.initials: JP
authors.lastname: Lee
authors.forename: Juhyun
authors.initials: J
authors.lastname: Kim
authors.forename: Seaung Youl
authors.initials: SY
authors.lastname: Oh
authors.forename: Myung-Kwan
authors.initials: MK
authors.lastname: Chun
authors.forename: Hoo-Kyun
authors.initials: HK
authors.lastname: Choi
mesh_terms: D000269:Adhesives / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D006724:Hoof and Claw / Q000378:metabolism*; D008566:Membranes / Q000378:metabolism*; D051379:Mice; D008812:Mice, Hairless; D009281:Naphthalenes / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010539:Permeability / Q000187:drug effects; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011312:Pressure; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects; D013552:Swine; D000077291:Terbinafine
chemical_list: D000269:Adhesives; D000935:Antifungal Agents; D009281:Naphthalenes; D014677:Pharmaceutical Vehicles; D000077291:Terbinafine